Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation.
Cell-cycle progression is regulated by cyclin-dependent kinases (CDKs). CDK1 and CDK2 can be also activated by noncyclin proteins named RINGO/Speedy, which were identified as inducers of the G2/M transition in Xenopus oocytes. However, it is unclear how XRINGO triggers M phase entry in oocytes. We show here that XRINGO-activated CDKs can phosphorylate specific residues in the regulatory domain of Myt1, a Wee1 family kinase that plays a key role in the G2 arrest of oocytes. We have identified three Ser that are major phosphoacceptor sites for CDK/XRINGO but are poorly phosphorylated by CDK/cyclin. Phosphorylation of these Ser inhibits Myt1 activity, whereas their mutation makes Myt1 resistant to inhibition by CDK/XRINGO. Our results demonstrate that XRINGO-activated CDKs have different substrate specificity than the CDK/cyclin complexes. We also describe a mechanism of Myt1 regulation based on site-specific phosphorylation, which is likely to mediate the induction of G2/M transition in oocytes by XRINGO.
Ruiz
E Josué
EJ
CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Hunt
Tim
T
Nebreda
Angel R
AR
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D019926:Cyclin B / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation; D016195:G2 Phase / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D009865:Oocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004268:DNA-Binding Proteins; C489725:Myt1 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; C119055:ls27 protein, Xenopus; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases